Translation of c-myc mRNA is required for its post-transcriptional regulation during myogenesis

During the differentiation of C2 myoblasts into differentiated myotubes, there is a marked decrease in the abundance of c-myc mRNA. c-myc transcription initiation and elongation do not change significantly, but the turnover of c-myc transcripts appears to be accelerated during differentiation. We examined the expression of several recombinant c-myc genes introduced into C2 cells by stable transfection and found that mRNAs containing the c-myc protein-coding region of exons 2 and 3 are appropriately regulated; the upstream c-myc sequences, the long leader sequence encoded by c-myc exon 1, and the 3' untranslated region are dispensible for proper regulation. Regulation appears to affect c-myc transcripts that are bound to polyribosomes, and the mRNA from a gene with a point mutation in the translation initiation codon is no longer properly regulated. We conclude that down-regulation of c-myc expression during myogenesis is post-transcriptional and requires the presence of sequences encoding the c-myc protein in a form that can be translated.